Persistent or chronic postsurgical pain (CPSP) has been defined as 'pain persisting beyond 2 months'. The cut-off limit of 2 months has been controversial, and some researchers argue for a 3-month period for the definition of CPSP. Multiple mechanisms, including both patient and surgical, have been shown to influence this transition. Patient factors include age, gender, anxiety, depression, somatisation, catastrophising, pre-existing pain anywhere and pain at the site of surgery. The various surgical factors include site and nature of surgery, infection, inflammation and repeat surgery. There is evidence that pre- or post-op chemotherapy and radiotherapy can also contribute towards the chronification of pain after surgery. The question of why pain following surgery or trauma persists long after the normal healing time is not yet fully explained by current evidence. This is frustrating to healthcare providers and intensely disappointing to the patients, many of whom suffer in silence for years. Genetics is now being shown to influence both the onset and the perpetuation of chronic pain in the susceptible patient. The main mechanisms are believed to be 'single nucleotide polymorphisms' (SNPs) and 'epigenetics', both of which will be discussed, with current and ongoing research and evidence, in this review. The influence of SNPs has not been replicated in recent studies and researchers advise caution in interpreting past studies. More research is needed to demonstrate the involvement of epigenetics as well as linking SNPs to the susceptible patient's journey.