In this review, we go over the main points of the evidence showing the critical role of p110δ PI3K in hematopoietic cells and malignancies, we highlight findings suggesting an emerging role of p110δ in non-hematologic cancers and discuss how a better understanding of p110δ regulation and function might reveal cancer contexts in which p110δ-selective inhibitors alone or in combination with inhibitors of other components of PI3K pathway could be beneficial. The gene discussed is PIK3CD; the disease is cancer.