The chemical identification and determination of any kind of forensic evidence are often required in illegality investigations or even in legal prosecutions, and represent the main goal of forensic chemistry. A variety of types, forms, and complexity of evidence are commonly analyzed in forensic chemistry by different analytical techniques, e.g., hair, blood, urine, saliva, drugs, food, beverages, documents, gunshot residue, explosives, fire residue, agrochemicals, among others. Paper spray ionization mass spectrometry (PSI-MS) is an ambient technique of ionization that provides results quickly with high accuracy, sensitivity and reproducibility, employing a simple, non-destructive, and low-cost sampling procedure, very relevant in analysis of evidence in the forensic chemistry field. In this chapter, the most important methodologies and applications of the PSI-MS will be presented and discussed involving the forensic chemistry analysis in illicit drugs such as marijuana, cocaine, hallucinogens and new psychoactive substances, among others; in addition, the evaluation of agrochemicals, food adulterants, documentoscopy, and explosives will be displayed.