Screening compounds precipitate out of high-concentration DMSO solutions and cause issues in the liquid-handling equipment used to process the samples as well as false-positives and false-negatives in the biological data. This report examines the extent of the precipitation issue, correlation with physico-chemical properties of compounds, and measured concentrations. Possible ways to allow recovery of the precipitated solids are also described. This study also investigated whether particulates were present from the time of initial solubilization in DMSO or whether precipitation occurs during freeze-thaw cycling.