Hyperbaric oxygen therapy (HBOT) involves patients breathing 100% oxygen in a pressurized chamber, above 1 atmosphere. Many centers are now promoting the use of HBOT for skin rejuvenation. However, the current indications for HBOT do not encompass aesthetic applications. The aim of this evidence-based review was to assess the existing literature regarding the utilization of HBOT in medical aesthetics and rejuvenation, evaluate its effectiveness and safety, and conduct a cost analysis. PubMed Interface, Cochrane Library, Google Scholar, and Embase searches were carried out. The Best Bets methodology was used, and the risk of bias was appraised using the Quality Assessment Tool for Quantitative Studies. This review included a total of 17 human studies with a total of 766 participants. Three studies were classified as level II evidence, three studies were of level III evidence, and 11 were of level IV evidence. All the included studies were judged at high risk of bias. The most relevant findings supported by level II evidence were that HBOT decreased the shedding rate post-FUE hair transplant (27.6 ± 2.6% vs. 69.1 ± 2.4%) but this did not affect the final outcome between HBOT (96.9 ± 0.5%) and the control (93.8 ± 0.6%). Moreover, level III evidence demonstrated that following HBOT, there was a significant increase in elastic fiber length (p ≤ 0.0001, effect size = 2.71) and a significant decrease in fiber fragmentation (p = 0.012). There was also a significant increase in collagen fiber density following HBOT (p = 0.0001, effect size = 1.10). However, there was no significant effect of antioxidant vitamins A, C, and E with HBOT. The inflammatory response significantly decreased after 7 days of HBOT with a decreased expression of IL-12p40, MIP-1β, and PDGF-BB and a higher expression of IL-1Ra. Moreover, HBOT was used prophylactically prior to abdominoplasty to decrease the risk of complications. In this study, complications were decreased from 32.6% (89 patients) to 8.4% (7 patients) with a p < 0.001, and in a multivariate analysis, preoperative HBOT was an independent protective factor against postoperative complications (p < 0.001). There is conflicting evidence on how the method of action of HBOT can have a beneficiary effect in aesthetic and whether the treatment is justifiable. To our knowledge, this is the first comprehensive review discussing the available evidence regarding the use of HBOT in many aesthetic clinical scenarios, including preventive, medical, and surgical settings. However, randomized clinical trials with longer follow-up and better patient selection are needed to be able to generate a reliable conclusion.