Globally, humans are harvesting the majority of capture fisheries at or above maximum sustainable yield, yet the demand for seafood is ever growing, a trend that cannot be met by the apparent plateau or possible decline of capture fisheries. Aquaculture appears to be an essential part of the solution, although it has become an increasingly controversial form of food production due to human health concerns and negative environmental impacts, as it has developed into a viable industry over the past 20 years. The US Department of Commerce is currently drafting legislation for the purpose of creating a streamlined permitting process for offshore aquaculture facilities in the US exclusive economic zone (EEZ). The objective of the legislation, referred to as the National Offshore Aquaculture Act of 2005, is to increase current US aquaculture production from a $1 billion per year industry to $5 billion annually by the year 2025. However, permitting aquaculture facilities in federal waters may have negative impacts on marine biodiversity in regards to increased disease transmission to wild stocks, pollution, escaped exotic or genetically modified species, as well as interference with natural marine mammal behavior and protected species. The purpose of this review is to evaluate the sustainability and feasibility of the US plan to intensity aquaculture efforts in the US EEZ through current case studies and interviews of industry experts and scientists, and to produce recommendations for a future policy framework based on the impacts to marine biodiversity. Given the many uncertainties, the Department of Commerce should consider the following limits to offshore aquaculture projects: 1) No aquaculture activities producing non-native species should be permitted in federal waters to protect wild species that may be at risk of hybridizing or losing habitat to nonendemic escapees; 2) A moratorium on genetically modified species should remain until their safety can be proven in land locked closures over several generations; 3) Antibiotics and pesticides should only be administered to fish in quarantine by a veterinarian, and mandatory reporting of therapeutic types and quantities used by offshore aquaculture farms will assist in public awareness and project transparency; 4) Pens should not be sited in areas that overlap with marine mammal activities that will cause disruption, stress, or disease to these animals in compliance with the Marine Mammal Protection Act; 5) Identify areas that will be restricted from offshore aquaculture activities that may pose additional stress to protected species or recovering wild fish stocks. Aquaculture exclusion zones should be determined in collaboration with fisheries management councils, and abide by the protections afforded by the Endangered Species Act.