Management of chronic pain is crucial to improve the quality of life of cancer and palliative care patients. Opioid-based treatments used to control pain can be prolonged over time. Unfortunately, constipation is one of the most disturbing adverse effects of long-term use of opioids. Opioid-induced constipation (OIC) occurs when opioids bind to the specific receptors present in the gastrointestinal (GI) tract, and can affect any patients receiving chronic opioid therapy, including cancer patients. The limited efficacy of laxatives to treat OIC symptoms prompted the search for new therapeutic strategies. Peripherally acting μ-opioid receptor antagonists (PAMORAs) have recently emerged as new effective drugs for OIC management due to their specific binding to enteric μ-receptors. Little information is available on the use of PAMORAs in real-life practice for OIC treatment in cancer patients. In this paper, a panel of experts specializing in cancer and palliative care pools their clinical experience with PAMORAs in cancer patients presenting OIC and highlights the importance of timing and choice of therapy in achieving prompt OIC management and benefitting patients.