For almost 15 years there has been stagnation in the systemic treatment of patients with pancreatic ductal adenocarcinoma (PDAC). Recently, several developments seem to indicate clinically relevant improvements in the treatment of patients with metastatic disease. One of these developments is the introduction of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) into the firstline treatment of metastatic disease. In this review, underlying preclinical and clinical data are discussed, with a special focus on mechanisms of action, the potential interaction with albumin and calcium-binding matricellular glycoproteins, such as the secreted protein acidic and rich in cysteine (SPARC), as well as the clinical outcome associated with the use of nab-paclitaxel.