With the advent of advancements in deep learning approaches, such as deep convolution neural network, residual neural network, adversarial network; U-Net architectures are most widely utilized in biomedical image segmentation to address the automation in identification and detection of the target regions or sub-regions. In recent studies, U-Net based approaches have illustrated state-of-the-art performance in different applications for the development of computer-aided diagnosis systems for early diagnosis and treatment of diseases such as brain tumor, lung cancer, alzheimer, breast cancer, etc., using various modalities. This article contributes in presenting the success of these approaches by describing the U-Net framework, followed by the comprehensive analysis of the U-Net variants by performing (1) inter-modality, and (2) intra-modality categorization to establish better insights into the associated challenges and solutions. Besides, this article also highlights the contribution of U-Net based frameworks in the ongoing pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also known as COVID-19. Finally, the strengths and similarities of these U-Net variants are analysed along with the challenges involved in biomedical image segmentation to uncover promising future research directions in this area.