Tamoxifen (ICI 46 474), trans-1-(4-β-dimethylaminoethoxyphenyl)-1,2-diphenylbut-1-ene, is the most commonly used drug for the treatment of estrogen receptor positive breast cancer and has been saving lives worldwide for the past four decades. Tamoxifen is considered a pioneering drug due to its ubiquitous use in both treatment and chemoprevention of breast cancer and also for research addressing novel selective estrogen receptor modulators (SERMs). Tamoxifen is cost effective, lifesaving, and devoid of major side effects in the majority of patients. The discovery of tamoxifen metabolites such as 4-hydroxy tamoxifen, N-desmethyl tamoxifen, and endoxifen has facilitated understanding of tamoxifen's and its metabolites' mechanisms of action in breast cancer therapy. Continuous efforts are being made by both industry and academia to synthesize novel tamoxifen derivatives in order to better understand the mechanism of this drug's action and to generate new agents with reduced side effects for many therapeutic targets. This review article comprises the tamoxifen derivatives reported in the literature in the last few years and we anticipate that it will assist medicinal chemists in the synthesis of novel and pharmacologically potent agents for various therapeutic targets. Display omitted •Tamoxifen is a pioneering drug for the treatment of ER-positive breast cancer cells.•Tamoxifen derivatives exhibited promising activity for cancer in addition to demonstrating other therapeutic activities.•Recent literature concerning synthesized tamoxifen derivatives and their pharmacological activities is reviewed.•The tamoxifen scaffold is an attractive target for the drug development.•The review will be useful for researchers who are developing novel tamoxifen derivatives aimed at several targets.