Prostate cancer detection is mainly based on PSA serum levels and digital rectal examination. The wide use of PSA with time led to increased prostate cancer incidence in the highest ressources countries worldwide with less mortality rates compared to less developed regions of the world. Screening for prostate cancer is among the most controversial topics in the field of urology. US Preventive Services Task Force recently finalized a crisp recommendation that routine PSA-based screening should be stopped. Results from the ERSPC study of screening for prostate cancer reported the impact of PSA testing in reducing cancer-specific mortality but with a higher rate of localized tumour detection with better prognostic factors. Scientific societies have elaborated their recommendations in favour of a share decision making with patients with at least 10 to 15 years of life expectancy. In view of the unsatisfactory accuracy of the two diagnostic exams, strategies to reduce PSA-driven prostate cancer overdiagnosis and overtreatment seem to be necessary. Research has focused on novel markers to improve pre-biopsy prostate cancer detection, such as prostate health index (phi) and PCA3. In patients with a total PSA range of 2-10 ng/ml, phi and PCA3 seem to be the strongest predictors of prostate cancer at initial biopsy and are significantly more accurate than total PSA and percentage free PSA.