The forensic process encompasses many stages from the initial investigation of a crime scene to the presentation of witness testimony in court. Most of the current analytical techniques used to analyze forensic evidence require a sample preparation prior to the analytical stage. This chapter provides an overview of the novel sample preparation modes, published up to date, for samples of forensic interest. This information has been grouped into the three following themes: explosives and related samples, drugs and toxicological analysis, and other forensic samples. The identification of explosives and related samples has become a heightened priority in recent years for homeland security and counterterrorism applications. The chapter also discusses drug analyses and forensic toxicology. A transition to noninvasive and nondestructive analysis avoiding any sample treatment is expected in the near future for most forensic evidence.