Resonant absorption of first-overtone (FO) CO laser radiation by atmospheric water vapor and various organic and nonorganic pollutants is discussed. Suitable ro-vibrational lines are selected for their potential use in traditional spectroscopic schemes of atmospheric pollution diagnostics. Nonlinear atmospheric absorption of intense multiline FO CO laser radiation is simulated and laser-induced changes in absorption spectra are demonstrated. Absorption coefficients of a few substances on several FO CO ro-vibrational lines are experimentally measured. A comparative analysis of spectral characteristics of an FO CO laser and an HF (DF) laser demonstrates that the potential of FO CO laser applications for spectroscopic detection of various molecular trace gases is greater than that of HF and DF lasers.