The observation that the relative importance of picophytoplankton is greatest in warm and nutrient‐poor waters was tested here based on a comprehensive review of the data available in the literature from oceanic and coastal estuarine areas. Results show that picophytoplankton dominate (≥50%) the biomass and production in oligotrophic (chlorophyll a [Chl a] < 0.3 mg m−3), nutrient poor (NO3 + NO2 < 1 µM), and warm (>26°C) waters, but represent <10% of autotrophic biomass and production in rich (Chl a > 5 mg m−3) and cold <3°C) waters. There is, however, a strong covariation between temperature and nutrient concentration (r = −0.95, P < 0.001), but the number of observations where both temperature and nutrient concentrations are available is too small to allow attempts to statistically separate their effects. The results of mesocosm nutrient addition experiments during summer in the Mediterranean Sea allowed the dissociation of the effects of temperature from those of nutrients on pico phytoplankton production and biomass and validated the magnitude at which picoplankton dominates (≥50%) autotrophic biomass and production obtained in the comparative analysis. The fraction contributed by picoplankton significantly declined (r2 = 0.76 and 0.90, respectively, P < 0.001) as total autotrophic production and biomass increased. These results support the increasing importance of picophytoplankton in warm, oligotrophic waters. The reduced contribution of picophytoplankton in warm productive waters is hypothesized here to be due to increased loss rates, whereas the dominance of picophytoplankton in warm, oligotrophic waters is attributable to the differential capacity to use nutrients as a function of differences in size and capacity of intrinsic growth of picophytoplankton and larger phytoplankton cells.