This review outlines the discovery and development of a novel series of 1-[4-2- aminoethoxy)phenylcarbonyl]-3,5-bis-(benzylidene)-4-piperidones (5-8) as potential drug candidates over the last 15 years in our laboratory. Many of these compounds demonstrate excellent cytotoxic properties and are often more potent than contemporary anticancer drugs. Two highly important features of many of these molecules are first, the greater tumour-selective toxicity and second, the ability of these molecules to act as modulators of multi-drug resistance. The modes of action of some of the potent compounds are by apoptosis induction, generation of reactive oxygen species, activation of certain caspases and affecting mitochondrial functions. These molecules also display promising antimalarial and antimycobacterial properties. In a short term toxicity study, these molecules are well tolerated in mice. Structure-activity relationships and a drug delivery system along with pharmacokinetic studies and metabolic stability of these compounds, have been presented. The positive characteristics associated with the series (5-8) warrant their further evaluations as candidate antineoplastic drug candidates.