Medicinal plants have long been used globally for the management and treatment of diverse disease conditions. They are endowed with diverse secondary metabolites responsible for the therapeutic effects they exhibit hence the possibility of discovering novel, effective and affordable therapeutic targets with limited side effects. Scientific investigation of these medicinal plants has witnessed an upsurge in recent times. Piliostigma thonningii (Schum Milne-Redhead) commonly known as ‘‘camel’s foot’’ and ‘‘monkey bread’’and locally as ‘‘kalgo’’ in Hausa, ‘‘Omukpakpa ajalu’’ in Igala, ‘‘abafe’’ in Yoruba, ‘‘nyihar’’ in Tiv, ‘‘mchekeche’’ in Swahili and ‘‘Kharub’’ in Arab is distributed widely in tropical and subtropical regions of Africa. The different parts of the plant are known for the treatment and management of dysentery, fever, respiratory ailments, snakebites, hookworm and skin diseases, and gastro-intestinal tract problems among others. Although promising scientific reports have been published on the various parts of P. thonningii, no review comprehensively summarizes its traditional uses, phytochemistry, pharmacology, and toxicology. Therefore, this review aims to provide a critical and comprehensive evaluation of the traditional uses, phytochemistry, pharmacological properties and toxicology of P. thonningii as well as offer suggestions for future investigations.