I'm of the opinion that Hephaistion's sudden death was what did him in. Alexander's Macedonian lifestyle was always pretty wild (they took binge drinking to a whole other level), but after his closest companion died, Alexander spiraled into self-destruction. This makes sense when we consider his self-image: he viewed himself as the reborn Akhilles, and Hephaision was his Patroklos. When Hephaistion died, as patroklos had died, Alexander was consumed by grief just as Akhilles had been consumed by grief. He even took the exact same steps, cutting his hair and slaughtering cattle and erecting a great pyre and seeking out enemies to indiscriminately slaughter as if in offering to the Gods. In short: he mimicked the reactions of Akhilles down to the details.
And then he sought death, because Akhilles cannot live when Patroklos has perished. He exhibited all the signs of someone who's self-destructive. His drinking became literally suicidal.
Some suspect he was poisoned, but I don't think poison was needed. Alexander essentially killed himself. And then he became immortal in the memory of mankind, just like his idol Akhilles. All in all, a fitting end.