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Although photodynamic therapy (PDT) has been used successfully to treat an assortment of different types of cancer, it has yet to reach the level of mainstream medicine on either side of the Atlantic. Unsubstantiated claims of PDT’s efficacy in the past may be part of the reason for this. However, perhaps the main obstacle to PDT’s endorsement by conventional medicine is the limited number of high-quality randomized controlled trials (RCTs) comparing it with relevant comparators for all meaningful outcomes, including effectiveness, safety, adverse events, quality of life, survival, and cost. Based on a Health Technology Assessment report on the current status of PDT and consultation with professional groups, specialist societies, and clinical study groups in the United Kingdom, this article explores the current clinical guidelines for use of PDT in cancer treatment and the dearth of supportive data from RCTs.