In this review, we discuss the design, structures and pharmacological effects of numerous series of drug conjugates containing ER ligands such as selective ER modulators (tamoxifen, 4-hydroxytamoxifen, endoxifen), selective ER degraders (ICI-164384) and ER agonists (estradiol) linked to diverse anti-cancer agents including histone-deacetylase inhibitors, DNA-alkylating agents, antimitotic agents and epidermal growth factor receptor inhibitors. This evidence concerns the gene ESR1 and cancer.