Pyrazolo[3,4-d]pyrimidines have become of significant interest for the medicinal chemistry community as a privileged scaffold for the development of kinase inhibitors to treat a range of diseases, including cancer. This fused nitrogen-containing heterocycle is an isostere of the adenine ring of ATP, allowing the molecules to mimic hinge region binding interactions in kinase active sites. Similarities in kinase ATP sites can be exploited to direct the activity and selectivity of pyrazolo[3,4-d]pyrimidines to multiple oncogenic targets through focussed chemical modification. As a result, pharma and academic efforts have succeeded in progressing several pyrazolo[3,4-d]pyrimidines to clinical trials, including the BTK inhibitor ibrutinib, which has been approved for the treatment of several B-cell cancers. In this review, we examine the pyrazolo[3,4-d]pyrimidines currently in clinical trials for oncology patients, as well as those published in the literature during the last 5 years for different anticancer indications.