Cephalopods (Mollusca: Cephalopoda) play an important role as keystone invertebrates in various marine ecosystems, as well as being a valuable fisheries resource. At the World Malacological Congress, held 21–28 July 2013 in Ponta Delgada, Azores, Portugal, a number of cephalopod experts convened to honour the contribution of the late Malcolm R. Clarke, FRS (1930–2013) to cephalopod research. Endorsed by the Cephalopod International Advisory Council (CIAC), the meeting discussed some of the major challenges that cephalopod research will face in the future. These challenges were identified as follows: (1) to find new ways to ascertain the trophic role and food web links of cephalopods using hard tissues, stable isotopes and novel concepts in theoretical ecology; (2) to explore new approaches to the study of cephalopod morphology; (3) to further develop cephalopod aquaculture research; (4) to find new ways to ascertain cephalopod adaptation and response to environmental change; (5) to strengthen cephalopod genetics research; and (6) to develop new approaches for cephalopod fisheries and conservation. The present paper presents brief reviews on these topics, followed by a discussion of the general challenges that cephalopod research is bound to face in the near future. By contributing to initiatives both within CIAC and independent of CIAC, the principle aim of the paper is to stimulate future cephalopod research.