Objective This study aimed to examine the validity of the Arabic version of the Depression Anxiety Stress Scale-21 (DASS-21) in 149 illicit drug users. Methods We calculated α coefficient, inter-item and item-total correlations, coefficients of reproducibility and scalability (CR and CS), item difficulty and discrimination indices. Results The DASS-21 had an acceptable reliability; but values of the CR and the CS were less than acceptable. Items varied in difficulty and discrimination; some items are candidates for elimination. Conclusion The DASS-21 is a probabilistic and not a deterministic measure of distress; it has problematic items and needs further investigations.