The trade in live ornamental fishes to be held as companion animals or displayed in public aquaria has an estimated global annual value of US$15–20 billion. Supply chains for ornamental pet fishes often involve many more parties than for fish farmed as food fishes, and at each stage, fishes are exposed to stressors including handling, confinement, crowding, mechanical disturbance, and poor water quality. If chronic, these stressors can compromise their immune system, making fishes more susceptible to pathogens. Mortality and morbidity from infectious disease can result in considerable welfare impacts and massive economic losses for the industry, and the range of infective agents seen in ornamental species is well documented. However, treating these diseases is not straightforward with practices varying greatly across the trade and with several approaches having unintended consequences, such as the emergence of resistant strains of pathogens. While disease treatments for a handful of fish species (e.g., koi, goldfish) have received focused research attention, for the home aquarium owner, there is an increasing reliance on products based on natural compounds which have received far less scientific attention. This review aims to highlight the gaps in our knowledge surrounding the range of disease treatments used across the ornamental pet fish trade, with a particular focus on freshwater tropical species destined for home aquaria. Consideration is given to the potential problems arising from these treatments, including microbial resistance and effects of treatments themselves on fish health and welfare.