Purpose of Review The hereditary spastic paraplegias (HSPs) are a group of disorders characterised by progressive lower limb weakness and spasticity. We address the challenges and controversies involved in the genetic diagnosis of HSP. Recent Findings There is a large and rapidly expanding list of genes implicated in HSP, making it difficult to keep gene testing panels updated. There is also a high degree of phenotypic overlap between HSP and other disorders, leading to problems in choosing the right panel to analyse. We discuss genetic testing strategies for overcoming these diagnostic hurdles, including the use of targeted sequencing gene panels, whole-exome sequencing and whole-genome sequencing. Personalised treatments for HSP are on the horizon, and a genetic diagnosis may hold the key to access these treatments. Summary Developing strategies to overcome the challenges and controversies in HSP may hold the key to a rapid and accurate genetic diagnosis.

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