Perineural invasion (PNI) occurring in non-melanoma skin cancers (NMSC) is associated with an increased risk of locoregional recurrence and reduced disease-free survival. This necessitates early and accurate diagnosis, appropriate risk-stratification and a clear management strategy. The diagnosis of PNI is based on careful clinical assessment, imaging and histopathology. Surgery, preferably with margin control, and definitive or adjuvant radiotherapy (ART) are established treatment strategies for PNI. Clinical uncertainty remains over the role of ART in incidental PNI. This review synthesises current literature to ascertain which clinicopathological features impart a higher risk to individuals with PNI in NMSC, in order to provide treatment algorithms, including the identification of patient subsets that are most likely to benefit from ART. This includes those with extratumoural PNI, involvement of larger-calibre nerves, tumour invasion beyond dermis, recurrent tumour or diffuse intratumoural spread. Patients with clinical PNI may be optimally managed by a multidisciplinary head and neck cancer service that is best placed to offer skull base surgery and intensity-modulated radiation therapy (IMRT). The management options presented are stratified by histological subtype and a new classification of PNI into low-risk, medium-risk and high-risk groups.