In agricultural systems, soil quality is thought of in terms of productive land that can maintain or increase farm profitability, as well as conserving soil resources so that future farming generations can make a living. Management practices which can modify soil quality include tillage systems and crop rotations. A major proportion of Australian cotton (Gossypium hirsutum L.) is grown on Vertosols (~75%), of which almost 80% is irrigated. These soils have high clay contents (40–80 g/100 g) and strong shrink–swell capacities, but are frequently sodic at depth and prone to deterioration in soil physical quality if incorrectly managed. Due to extensive yield losses caused by widespread deterioration of soil structure and declining fertility associated with tillage, trafficking, and picking under wet conditions during the middle and late 1970s, a major research program was initiated with the objective of developing soil management systems which could improve cotton yields while concurrently ameliorating and maintaining soil structure and fertility. An outcome of this research was the identification of cotton–winter crop sequences sown in a 1 : 1 rotation as being able to sustain lint yields while at the same time maintaining soil physical quality and minimising fertility decline. Consequently, today, a large proportion (~75%) of Australian cotton is grown in rotation with winter cereals such as wheat (Triticum aestivum L.), or legumes such as faba bean (Vicia faba L.). A second phase of research on cotton rotations in Vertosols was initiated during the early 1990s with the main objective of identifying sustainable cotton–rotation crop sequences; viz. crop sequences which maintained and improved soil quality, minimised disease incidence, facilitated soil organic carbon sequestration, and maximised economic returns and cotton water use efficiency in the major commercial cotton-growing regions of Australia. The objective of this review was to summarise the key findings of both these phases of Australian research with respect to soil quality and profitability, and identify future areas of for research. Wheat rotation crops under irrigated and dryland conditions and in a range of climates where cotton is grown can improve soil quality indicators such as subsoil structure, salinity, and sodicity under irrigated and dryland conditions, while leguminous crops can increase available nitrogen by fixing atmospheric nitrogen, and by reducing N volatilisation and leaching losses. Soil organic carbon in most locations has decreased with time, although the rate of decrease may be reduced by sowing crop sequences that return about 2 kg/m2.crop cycle of residues to the soil, minimising tillage and optimising N inputs. Although the beneficial effects of soil biodiversity on quality of soil are claimed to be many, except for a few studies on soil macrofauna such as ants, conclusive field-based evidence to demonstrate this has not been forthcoming with respect to cotton rotations. In general, lowest average lint yields per hectare were with cotton monoculture. The cotton–wheat systems generally returned higher average gross margins/ML irrigation water than cotton monoculture and other rotation crops. This indicates that where irrigation water, rather than land, is the limiting resource, cotton–wheat systems would be more profitable. Recently, the addition of vetch (Vicia villosa Roth.) to the cotton–wheat system has further improved average cotton yields and profitability. Profitability of cotton–wheat sequences varies with the relative price of cotton to wheat. In comparison with cotton monoculture, cotton–rotation crop sequences may be more resilient to price increases in fuel and fertiliser due to lower overall input costs. The profitability of cotton–rotation crop sequences such as cotton–wheat, where cotton is not sown in the same field every year, is more resilient to fluctuations in the price of cotton lint, fuel and nitrogen fertiliser. This review identified several issues with respect to cotton–rotation crop sequences where knowledge is lacking or very limited. These are: research into ‘new’ crop rotations; comparative soil quality effects of managing rotation crop stubble; machinery attachments for managing rotation crop stubble in situ in permanent bed systems; the minimum amount of crop stubble which needs to be returned per cropping cycle to increase SOC levels from present values; the relative efficacy of C3 and C4 rotation crops in relation to carbon sequestration; the interactions between soil biodiversity and soil physical and chemical quality indicators, and cotton yields; and the effects of sowing rotation crops after cotton on farm and cotton industry economic indicators such as the economic incentives for adopting new cotton rotations, farm level impacts of research and extension investments, and industry- and community/catchment-wide economic modelling of the impact of cotton research and extension activities.