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In the quest to developing novel cancer therapies, oncolytic Clostridia are re-emerging as promising candidates due to their ability to specifically target and lyse tumours with great efficacy. Clostridial spores have the innate abilities that exploit the unique tumour microenvironment by directly penetrating, colonising and killing tumour cells. These unique features have prompted many studies to investigate their oncolytic potency. In addition, Clostridia possess a number of characteristics that enable them to be developed as oncolytic gene delivery vectors, such as their unlimited capacity, antibiotic sensitivity, and extracellular existence. Similarly, numerous strategies are being devised and tested to take advantage of these features with modern molecular technologies. In this review, we detail the traits that distinguish Clostridia from other agents, and describe the potential therapeutic effects that Clostridial spores demonstrate, but are not achievable with other treatment modalities. Furthermore, we will also summarize the recent advances in the use of Clostridial spores as viable therapeutic candidates, incorporating the latest progresses in genetic engineering tools, such as ClosTron. Finally, we will highlight some avenues deserving further studies in order to realise the ultimate goal of utilizing oncolytic Clostridia clinically in patients.