Non-melanomatous skin cancers (NMSCs) are the most common cancers affecting humans. Basal cell (BCC) and squamous cell carcinomas (SCC) make up the vast majority of NMSCs and both increase in incidence with age. As populations age worldwide, NMSC rates are continuing to increase, emphasizing the importance of a thorough understanding of these two tumours, their presentation, clinicopathologic variants, classification, management and follow-up in modern clinical practice. Recent developments in mutational profiling and improved understanding of the molecular mechanisms underlying the aetiology of these tumours has led to the development of targeted therapies. Novel therapies showing early promise such as systemic inhibitors of the Hedgehog pathway in BCC are reviewed in light of existing treatments so as to provide an evidence-based approach to their management.