Freshwater sponges (Spongillida: Demospongiae), including more than 240 described species, are globally distributed in continental waters (except for Antarctica), where they cover both natural and artificial surfaces. However, fragmentary studies have targeted their microbiome, making it difficult to test hypotheses about sponge-microbe specificity and metabolic relationships, along with the environmental factors playing key roles in structuring the associated microbial communities. To date, particular attention has been paid to sponges (family Lubomirskiidae) that are endemic to Lake Baikal. Few other freshwater sponge species (e.g., Ephydatia spp., Eunapius spp., and Spongilla lacustris), from lakes and rivers spanning from Europe to South and North America, have been targeted for microbiological studies. Representatives of the phyla Proteobacteria, Bacteroidetes, and Actinobacteria largely predominated, and high differences were reported between the microbiome of freshwater and marine sponges. Several bacterial strains isolated from freshwater sponges can produce bioactive compounds, mainly showing antibiotic activities, with potential application in biotechnology. Understanding the roles played by sponge microbiomes in freshwater ecosystems is still in its infancy and has yet to be clarified to disentangle the ecological and evolutionary significance of these largely under-investigated microbial communities. This review was aimed at providing the main available information on the composition and biotechnological potential of prokaryotic communities associated with healthy freshwater sponges, as a neglected component of the global sponge microbiome, to stimulate researchers interested in the field.