Aim and objective: To review the status of various approaches for prophylaxis of coronavirus disease-2019 (COVID-19). Background: The extensive spread of the novel COVID-19 has seen tremendous success over the span of few months. In comparison, our progress in developing an adequate treatment or preventive modality has been sluggish, at most. Results: Many observational studies and clinical trials are published evaluating chloroquine and hydroxychloroquine as prophylactic measures for COVID-19. Some question its safety, some refute its use while some uphold its beneficial effect. Although some scientific bodies advocated its routine use in some population without adequate evidence, current consensus proposes its prophylactic use in the context of clinical research only. Apart from chemotherapeutic drugs, several vaccines are under various phases of clinical development. Innovative vaccine development faces many hurdles as do the new drugs—from the inception of concept and establishing manufacturing process to time-consuming preclinical and clinical development, regulatory processes, large scale production, and then marketing. There is a lot of hopes and expectations from AstraZeneca's candidate vaccine, ChAdOx1-S, and Serum Institute of India's recombinant bacille Calmette–Guerin that are currently in phase III clinical trial. In order to expedite vaccine development, controlled human infection models are also being explored. Some research bodies also suggest using complementary and alternative medicine to supplement the existing and novel prophylactic therapies in preventing the infection. Conclusion and clinical significance: The increase in literature on the management of COVID-19 reflects the demand to address the current pandemic. At the same time, it becomes critical that research community works toward providing best evidence for guiding the clinicians’ practice and that clinicians and regulators emphasize on appraising the existing evidence before prescribing and making policies, respectively.