Photoacoustic imaging (PAI), recognized as a promising biomedical imaging modality for preclinical and clinical studies, uniquely combines the advantages of optical and ultrasound imaging. Despite PAI’s great potential to provide valuable biological information, its wide application has been hindered by technical limitations, such as hardware restrictions or lack of the biometric information required for image reconstruction. We first analyze the limitations of PAI and categorize them by seven key challenges: limited detection, low-dosage light delivery, inaccurate quantification, limited numerical reconstruction, tissue heterogeneity, imperfect image segmentation/classification, and others. Then, because deep learning (DL) has increasingly demonstrated its ability to overcome the physical limitations of imaging modalities, we review DL studies from the past five years that address each of the seven challenges in PAI. Finally, we discuss the promise of future research directions in DL-enhanced PAI.