Among cell death regulators, members of the Bcl-2 family are of interest because they are highly conserved across species and represent promising targets for anticancer therapy. This family and its associated proteins include more than 25 members, with either anti- or proapoptotic functions. Although the overall regulation of apoptosis by Bcl-2 family proteins is now well understood, targeted therapy requires careful consideration of individual members of the family and their crosstalk. One of the most studied representatives of the Bcl-2 family is antiapoptotic Mcl-1. After 25 years of investigations, a large amount of data regarding Mcl-1's regulation and functions has been compiled. In this review, we summarize current knowledge about Mcl-1, focusing on molecular aspects relevant to Mcl-1-targeted therapies.