Simple Summary Olivacine is a compound isolated from the bark of Aspidosperma olivaceum (a tree found mainly in Southeastern Brazil) that shows multidirectional biological activity. The most important of them is the antiproliferative effect, important in anticancer therapy. This article reviews the literature on the results of research on olivacine and its derivatives carried out in cell laboratories, in preclinical studies in animals and clinical trials in humans. The described activities of these compounds were discussed by comparing the differences in their structure. The most important finding of this review is that some olivacine derivatives exhibit greater anticancer activity than doxorubicin (a commonly used anticancer drug). Olivacine and its derivatives are characterized by multidirectional biological activity. Noteworthy is their antiproliferative effect related to various mechanisms, such as inhibition of growth factors, enzymes, kinases and others. The activity of these compounds was tested on cell lines of various tumors. In most publications, the most active olivacine derivatives exceeded the effects of doxorubicin (a commonly used anticancer drug), so in the future, they may become the main new anticancer drugs. In this publication, we present the groups of the most active olivacine derivatives obtained. In this work, the in vitro and in vivo activity of olivacine and its most active derivatives are presented. We describe olivacine derivatives that have been in clinical trials. We conducted a structure-activity relationship (SAR) analysis that may be used to obtain new olivacine derivatives with better properties than the available anticancer drugs.