The lower cloud layer of Venus (47.5–50.5 km) is an exceptional target for exploration due to the favorable conditions for microbial life, including moderate temperatures and pressures (∼60°C and 1 atm), and the presence of micron-sized sulfuric acid aerosols. Nearly a century after the ultraviolet (UV) contrasts of Venus' cloud layer were discovered with Earth-based photographs, the substances and mechanisms responsible for the changes in Venus' contrasts and albedo are still unknown. While current models include sulfur dioxide and iron chloride as the UV absorbers, the temporal and spatial changes in contrasts, and albedo, between 330 and 500 nm, remain to be fully explained. Within this context, we present a discussion regarding the potential for microorganisms to survive in Venus' lower clouds and contribute to the observed bulk spectra. In this article, we provide an overview of relevant Venus observations, compare the spectral and physical properties of Venus' clouds to terrestrial biological materials, review the potential for an iron- and sulfur-centered metabolism in the clouds, discuss conceivable mechanisms of transport from the surface toward a more habitable zone in the clouds, and identify spectral and biological experiments that could measure the habitability of Venus' clouds and terrestrial analogues. Together, our lines of reasoning suggest that particles in Venus' lower clouds contain sufficient mass balance to harbor microorganisms, water, and solutes, and potentially sufficient biomass to be detected by optical methods. As such, the comparisons presented in this article warrant further investigations into the prospect of biosignatures in Venus' clouds.