Abstract Atmospheric pressure chemical ionization (APCI) has been commercially implemented in gas chromatography mass spectrometry (GC-MS) instruments within the past decade and is becoming an important complementary tool to traditional GC-electron impact (EI) ionization-MS and liquid chromatography MS (LC-MS) for quantitative and nontarget screening purposes. APCI is a soft ionization technique, so more molecular ions and/or protonated molecules are present than when the traditional EI source is implemented, improving the sensitivity and selectivity of analytical methods. Moreover, this state-of-the-art apparatus facilitates the identification of chemicals not contained in commercial libraries. In this review, parameters inside and outside the APCI source could influence the sensitivity of the analysis are discussed. Trends towards improvement of APCI source and combination with multidimensionality further improve the quantitative and qualitative analysis of GC-MS. Finally, the applications of GC-APCI-MS, especially in nontarget studies are addressed.