Increasing societal and customer pressure to provide animals with ‘a life worth living’ continues to apply pressure on livestock production industries to alleviate pain associated with husbandry practices, injury and illness. Over the past 15–20 years, there has been considerable research effort to understand and develop mitigation strategies for painful husbandry procedures in sheep, leading to the successful launch of analgesic approaches specific to sheep in a number of countries. However, even with multi-modal approaches to analgesia, using both local anaesthetic and non-steroidal anti-inflammatory drugs (NSAID), pain is not obliterated, and the challenge of pain mitigation and phasing out of painful husbandry practices remains. It is timely to review and reflect on progress to date in order to strategically focus on the most important challenges, and the avenues which offer the greatest potential to be incorporated into industry practice in a process of continuous improvement. A structured, systematic literature search was carried out, incorporating peer-reviewed scientific literature in the period 2000–2019. An enormous volume of research is underway, testament to the fact that we have not solved the pain and analgesia challenge for any species, including our own. This review has highlighted a number of potential areas for further research.