With over 500 individual compounds, the Amaryllidaceae alkaloids represent a large and structurally diverse group of phytochemicals. Coupled to this structural diversity is the significant array of biological properties manifested by many of its members, of which their relevance in motor neuron disease and cancer chemotherapy has attracted considerable attention. To this extent, galanthamine has evolved into a successful commercial drug for Alzheimer's disease since its approval by the FDA in 2001. Concurrently, there have been several positive indicators for the emergence of an anticancer drug from the Amaryllidaceae due to the potency of several of its representatives as cell line specific antiproliferative agents. In this regard, the phenanthridones such as pancratistatin and narciclasine have offered most promise since their advancement into clinical trials, following which there has been renewed interest in the cytotoxic properties of these alkaloids. Given this background, this review seeks to highlight the various mechanisms which have been invoked to corroborate the cytotoxic effects of Amaryllidaceae alkaloids.