Orochimaru was one of the first major villains to be introduced in Naruto, nearly destroying the Leaf Village and being responsible for Sasuke's desertion from it. As of the current point in Boruto, he's still alive and kicking, while nearly every other villain in Naruto and Naruto Shippuden is gone.
This is partially because Orochimaru has ceased his hostilities towards the village, but is also due to his cheating death multiple times. So how has he been able to do it?
Orochimaru's Quest
Orochimaru was once one of the most powerful ninja serving the Hidden Leaf Village, but sought immortality in order to achieve his true quest of uncovering all the world's secrets. Painfully aware that a single human lifespan is far too short to achieve this, he began experimenting on fellow ninja. Orochimaru eventually developed a crude means to achieve this end.
The Immortality Jutsu Orochimaru developed involves not extending his own body's life but forcibly transferring his soul into other bodies and taking them over. The process involves him transforming into a giant white snake, his true form. Orochimaru's mind remains intact while he switches bodies somewhat regularly. After he switches bodies, he uses a variety of techniques to maintain his original appearance on the surface. Orochimaru seems to be able to use the technique on almost anyone, but can only attempt it once every three years, and prefers to plant a curse mark on his favored victims.The exact mechanisms and criteria for pulling off the Immortality Jutsu are poorly explained, but it does have some significant weaknesses.
To begin with, some hosts for the technique are more ideal than others. In Part 1, Orochimaru sought out Sasuke Uchiha to be his host, believing that the boy was powerful enough to grant him a full second life, as well as wanting control of his Sharingan eye. Sasuke didn't make it to him in time, and he was forced to use the body of a prisoner, which began to reject him after three years. This made Orochimaru grow gradually weaker over time once again, and Sasuke took advantage of that weakness to seemingly kill him when he attempted the jutsu again.
In reality, Sasuke's Sharingan reversed the jutsu, and Orochimaru was absorbed into the curse mark which he himself planted on Sasuke. During Sasuke's battle against his brother Itachi, Orochimaru managed to emerge from the curse mark, but was immediately sealed by the mythical Totsuka Blade, which Itachi controls. Orochimaru seemed gone for good, but Sasuke willingly revived him by removing his consciousness from another former student, Leaf Ninja Anko Mitarashi's curse mark. He then revealed that he'd observed much of the interceding events between that point and Sasuke and Itachi's battle through said curse mark, meaning his consciousness never died. Thus it seems as long someone lives with a curse mark from Orochimaru, he never truly dies. The fact that Sasuke revived him, however, seems to suggest that he cannot do so himself in this state.
Why Orochimaru is Almost Impossible to Kill
The Immortality Jutsu is only one way Orochimaru keeps himself alive, but modifications to his bodies also play a big role in this. Orochimaru is capable of regeneration to a frightening degree, being able to effortlessly restore lost limbs and even regurgitate an intact new body if he gets severely injured. Sasuke refers to these techniqes as the Power of the White Snake. These techniques do take up a great deal of chakra and thus Orochimaru can't use them infinitely, but he doesn't need to. Orochimaru is even by current standards one of the strongest ninja in the series, or ever to exist.
Even with the use of his arms (and thus jutsu) cut off by the Third Hokage and severely weakened, he held his own against fellow Sannin Tsunade and Jiriaya and defeated Naruto in Tailed Beast Version 2. The Akatsuki, of which he was once a member, continued to see him as a genuine threat. Since having his jutsu restored, Orochimaru is even more powerful than before, and fought the powerful Kara member Victor evenly in Boruto.
Orochimaru's sheer power combined with his regenerative capabilities and Immortality Jutsu make him it nearly impossible for him to die, and thus he hasn't. He has, however, taken a more humane course in his experimentation since he became interested in Sasuke's natural development after his battle with Itachi, and is now an occasional ally of the Leaf Village.