Pain is a common distressing symptom in children receiving pediatric palliative care. Both in children with cancer, but especially in children with progressive neurodegenerative and chromosomal conditions with CNS impairment pain is common, and often under-recognized and undertreated. Multimodal analgesia for children with serious illness acts synergistically for more effective pediatric pain and symptom control with fewer side effects than a single analgesic or modality. Successful pain treatment and prevention usually include integrative 'nonpharmacological' therapies, rehabilitation, psychology and spirituality in addition to pharmacology and regional anesthesia. This review article will address these effective components of multimodal pediatric analgesia and present starting doses of basic analgesia, opioids and adjuvants analgesia in infants, children and adolescents with serious illness.