The interest in research on up-flow anaerobic sludge blanket (UASB) reactors is growing. The meta-analysis of bibliometric data highlighted the growing interest in four diverse topics: (i) energy recovery production; (ii) combination with other treatments; (iii) the study of processes for the removal of specific pollutants and, (iv) characterization of microbial community and granular sludge composition. In particular, the papers published in the first 6 months of 2021 on this process were selected and critically reviewed to highlight and discuss the results, the gaps in the literature and possible ideas for future research. Although the state of research on UASB is to be considered advanced, there are still several points that will be developed in future research such as the consolidation of the results obtained on a semi-industrial or real scale, the use of real matrices instead of synthetic ones and a more in-depth study of the effect of substances such as antibiotics on the microbiota and microbiome of UASB granular biomass. To date, few and conflicting data about the environmental footprint of UASB are available and therefore other studies on this topic are strongly suggested.