The Middle Stone Age (MSA) sequence at Sibudu Cave, KwaZulu-Natal, South Africa, includes pre-Still Bay, Still Bay and Howiesons Poort assemblages that pre-date 60 ka. More recent MSA lithic assemblages have ages of ~58 ka, ~48 ka and ~38 ka derived from luminescence dating of quartz grains. Discrete hearths and ash-patches are present throughout, while palimpsests of hearths characterise the ~48 ka occupations. The people who lived at Sibudu were skilled encounter-hunters who killed a wide range of animals of all sizes. Their prey included zebra and dangerous animals such as buffalo and bushpig. Unifacially or bifacially retouched lithic points were parts of weapons for hunting, but, sometimes, points seem to have been used as butchery implements. Use-trace analysis supports both interpretations. Points were absent during the Howiesons Poort Industry when small animals, from moist, evergreen forests, were the focus of hunters whose toolkits contained backed stone implements and worked bone. Bedding made from sedges seems present throughout the sequence. The environmental setting for cultural activities changed through time. Combined evidence from magnetic susceptibility, phytoliths, charcoal, pollen, seeds, mineralogy, macromammals and micromammals suggests that cold Marine Isotope Stage 4 (MIS 4) and warmer MIS 3 conditions are represented at the site. The changing temperatures, moisture availability and distance from the coast during MIS 4 and MIS 3 influenced vegetation, sediments and animal populations. Much of the sequence from ~58 ka onwards was associated with open grassland and with more large grazers than is the case in the area today. Proportions of evergreen and deciduous taxa fluctuated, with an increase of deciduous taxa possibly coinciding with warmer temperatures and increased evapotranspiration at ~48 ka.