This paper reviews the issues associated with algal–cyanobacterial taste–odour (T&O) compounds and toxins in the Great Lakes. As with other remediated water bodies, the Great Lakes have undergone significant shifts in nutrient and food-web regimes and are exhibiting erratic blooms and noxious algal metabolite (NAM) outbreaks, despite reduced offshore nutrient levels. We appraise the chemistry, biota, and distribution of NAM impairments and conclude that management strategies based on lakewide monitoring and remedial action plans are often unsuccessful because they attempt NAM control through an unsustainable reliance on water treatment and broad-scale nutrient–biomass models. This approach is undermined by several factors: (i) only some species produce NAMs; (ii) different taxa show disparate patterns across nutrient and mixing regimes; (iii) nuisance species may be planktonic or benthic and located outside remedial boundaries; and (iv) species differ significantly in NAM biochemistry and release. Thus, there are no robust relationships between total plankton biomass, toxins, and T&O compounds in these and other source waters. Given the potential ecological and socioeconomic threats posed by NAM outbreaks, there is a critical need to develop a multistep management framework based on more stringent restoration targets, combining broad-scale screening and nutrient management with system and taxa-specific approaches.