The use of bioactive glasses in dentistry, reconstructive surgery, and in the treatment of infections can be considered broadly beneficial based on the emerging literature about the potential bioactivity and biocompatibility of these materials, particularly with reference to Bioglass^® 45S5, BonAlive^® and 19-93B3 bioactive glasses. Several investigations have been performed (i) to obtain bioactive glasses in different forms, such as bulk materials, powders, composites, and porous scaffolds and (ii) to investigate their possible applications in the biomedical field. Although in vivo studies in animals provide us with an initial insight into the biological performance of these systems and represent an unavoidable phase to be performed before clinical trials, only clinical studies can demonstrate the behavior of these materials in the complex physiological human environment. This paper aims to carefully review the main published investigations dealing with clinical trials in order to better understand the performance of bioactive glasses, evaluate challenges, and provide an essential source of information for the tailoring of their design in future applications. Finally, the paper highlights the need for further research and for specific studies intended to assess the effect of some specific dissolution products from bioactive glasses, focusing on their osteogenic and angiogenic potential.