© The Royal Society of Chemistry. The portable electronic market, vehicle electrification (electric vehicles or EVs) and grid electricity storage impose strict performance requirements on Li-ion batteries, the energy storage device of choice, for these demanding applications. Higher energy density than currently available is needed for these batteries, but a limited choice of materials for cathodes remains a bottleneck. Layered lithium metal oxides, particularly those with high Ni content, hold the greatest promise for high energy density Li-ion batteries because of their unique performance characteristics as well as for cost and availability considerations. In this article, we review Ni-based layered oxide materials as cathodes for high-energy Li-ion batteries. The scope of the review covers an extended chemical space, including traditional stoichiometric layered compounds and those containing two lithium ions per formula unit (with potentially even higher energy density), primarily from a materials design perspective. An in-depth understanding of the composition-structure-property map for each class of materials will be highlighted as well. The ultimate goal is to enable the discovery of new battery materials by integrating known wisdom with new principles of design, and unconventional experimental approaches (e.g., combinatorial chemistry).