Microalgae have much higher lipid yields than those of agricultural oleaginosous crops, and they do not compromise arable land. Despite this, current microalga-based processes suffer from several constraints pertaining to the biocatalyst and the bioreactor, which hamper technologically and economically feasible scale-up. Here, we briefly review recent active research and development efforts worldwide, and discuss the most relevant shortcomings of microalgal biofuels. This review goes one step further relative to related studies, because it tackles otherwise scarcely mentioned issues for example, heterotrophic versus autotrophic metabolism, alkane versus glyceride synthesis, conduction versus bubbling of CO(2), and excretion versus accumulation of lipids. Besides promising solutions that have been hypothesized and arise from multidisciplinary approaches, we also consider less conventional ones. Microalgae and biofuels hold indeed a promising partnership, but a fully competitive technology is not expected to be available before the end of this decade, because the need for one order of magnitude increase in productivity requires development of novel apparatuses and transformed cells.