Diseases are natural components of the environment, and many have economic implications for aquaculture and fisheries. Aquaculture is a fast-growing industry with the aim to meet the high protein demand of the ever-increasing global population; however, the emergence of diseases is a major setback to the industry. Probiotics emerged as a better solution to curb the disease problem in aquaculture among many alternatives. Probiotic Bacillus has been proven to better combat a wide range of fish pathogens relative to other probiotics in aquaculture; therefore, understanding the various mechanisms used by Bacillus in combating diseases will help improve their mode of action hence yielding better results in their combat against pathogens in the aquaculture industry. Thus, an overview of the mechanisms (production of bacteriocins, suppression of virulence gene expression, competition for adhesion sites, production of lytic enzymes, production of antibiotics, immunostimulation, competition for nutrients and energy, and production of organic acids) used by Bacillus probiotics in mitigating fish pathogens ranging from Aeromonas, Vibrio, Streptococcus, Yersinia, Pseudomonas, Clostridium, Acinetobacter, Edwardsiella, Flavobacterium, white spot syndrome virus, and infectious hypodermal and hematopoietic necrosis virus proven to be mitigated by Bacillus have been provided.