Seaweed resources play an increasingly important role in European Blue Growth and Bioeconomy strategies and European production is anticipated to increase dramatically with the continued up-swing of global market interests in seaweed resources. As a consequence, there is a need to ensure the environmental sustainability of future aquaculture activities, as reported in the PEGASUS white paper. The present article summarizes the published PEGASUS guidelines developed in the framework of the COST Action Phycomorph, for the future development of this sector. This includes the advances made in this important arena of applied phycology taking into account scientific, technical, environmental, legal and socioeconomic dimensions. Challenges, bottlenecks and risks are identified and presented with a special focus on production issues regarding productivity, breeding, choice of appropriate cultivars, disease and pests and also the risk of using non-indigenous and invasive species as candidates for cultivation. The barriers for long-term, sustainable exploitation are also examined including harmony with the European “Nutrition and Health Regulations” necessary in order to ensure food safety. The PEGASUS guidelines provide scientific recommendations required to address the above issues and to provide science-based advice to policymakers, managers and industries for the sustainable development of industrial-scale seaweed aquaculture in Europe and beyond.