Cortistatins are a family of steroidal alkaloids with a unique pentacyclic skeleton, having immensely potent anti-angiogenetic activities. Given the scarcity in the natural availability of these compounds, their syntheses became major attractions in organic chemistry. Along with total synthesis of the most potent congeners in the family: cortistatins A and J, the synthesis of two other members have been successfully completed, while various other analogues have also been designed with variable degrees of biological activities. This review is an exhaustive coverage of the significant attempts towards constructing this highly challenging molecule and also aims to highlight the deep understanding of the structure-activity relationships of these compounds, which have been garnered over time.