The glutathione S-transferase (GST) family of enzymes is known to play a pivotal role in phase II of biotransformation of xenobiotics, environmental carcinogens and pharmacological drugs. The objective of the present study was to investigate the role of GSTM1 and GSTT1 null genotypes as risk factors for chronic obstructive pulmonary disease (COPD) and prostate cancer. The subjects appraised were 200 COPD cases, 150 prostate cancer cases, 150 benign prostatic hyperplasia (BPH) cases, 200 age matched controls for COPD and 172 age matched controls for prostate cancer. GSTM1 and GSTT1 null genotype was found to confer 2.5 (OR 2.45; 95% CI 1.56-3.82; P value = 0.00008) and 2.4-fold (OR 2.39; 95% CI 1.36-4.20; P value = 0.002) significant higher risk for prostate cancer. Smoking imparted a 2.2-fold significant risk of prostate cancer cases (OR 2.23; 95% CI 1.36-3.65 P value = 0.001) and twofold risk in BPH (OR 2.09; 95% CI 1.26-3.46; P value = 0.005). In case of COPD only null genotype of GSTT1 has shown 2.1-fold (OR 2.11; 95% CI 1.22-3.62; P value = 0.007) significant increased risk.