Two approaches may be utilized to explain the predominance of picocyanobacteria (Pcy) in oligotrophic lakes: the analysis of their interannual evolution in one single lake and their relative importance in different lakes along a trophic gradient. Here we discuss results from field data on picocyanobacteria over several seasons from a deep oligotrophic subalpine lake - Lago Maggiore, and variables influencing their abundance. Comparing data from lakes along a trophic gradient, no simple relationship emerges between lake’s trophic state and picocyanobacteria abundance and contribution to total phytoplanktonic biomass. That is, trophic state alone cannot explain the success/absence of picocyanobacteria that appear to be favored under P limitation, but seem more sensitive to grazing pressure and light. In some oligotrophic lakes, if light climate, grazing, and competition are favorable, picocyanobacteria can grow rapidly, out-compete competitors and become very abundant, but there are a host of factors that can influence the outcome of this competition, and ultimately influence Pcy success in lakes of all trophic types.