Prostate imaging techniques have progressed across the years allowing for a better detection and characterization of prostate cancer (PCa) lesions. These advancements have led to the possibility to also improve and tailor the treatments on the most aggressive lesion, defined as Index Lesion (IL), to reduce morbidity. The IL is, indeed, considered as the entity which encompass the most aggressive features in prostate cancer disease. Multiparametric magnetic resonance imaging (mpMRI) has emerged as the suggested tool to detect the disease and plan treatments, including those under investigation such as focal therapy (FT). Our review aimed to query the literature on the ability of mpMRI in IL detection and to explore the future perspectives in PCa IL diagnosis. A review of the literature was performed from January 2010 to July 2023. All studies investigating the performance of mpMRI and other main imaging techniques able to detect the IL were assessed and evaluated. mpMRI performs well in the detection of IL with a sensitivity which reaches 71% to 94% among the different studies. However, mpMRI seems to have limited sensitivity in the detection of small tumours (<0.5 mL) and low-grade histology lesions. To overcome these limitations other diagnostic imaging techniques have been proposed. Multiparametric Ultrasound has shown results comparable to mpMRI while detecting 4.3% fewer clinically significant PCa (P=0.042). Positron emission tomography-based modalities using PSMA seems to have higher sensitivity than mpMRI, being able to yield from 13.5% to 18.2% additional cancers. MRI has emerged as the recommended tool since most of the IL can be easily identified, and is the imaging of choice while selecting patients for FT. Other imaging modalities has been proposed to improve PCa lesions detection, but results need to be confirmed by ongoing randomized controlled trial.