Beginning from the premise that organisms must ‘eat, retreat, and excrete’ to survive, Amoebic Self Theory (AST) posits that humans also struggle for survival of the psychological sense of self – engulfing that which is desirable, resisting external threats, and disposing that which is toxic or redundant. These motives manifest across three related but distinct domains – the bodily, the social, and the spatial-symbolic – as facilitated by a boundary that differentiates ‘self’ from ‘not-self’. AST-inspired research has demonstrated both situational and chronic variation in the strength of these motives across domains, as well as their relevance to a breadth of diverse phenomenon, although advocates of other theoretical perspectives have focused primarily on the ‘dust mites experiment’. After considering their interpretations and claims, a case is made for AST as an integrative, generalist theory that generates novel predictions.