This chapter argues for the centrality of the natural sciences in the Scottish Enlightenment. Beginning in the mid-seventeenth century, the activities of mathematical practitioners such as George Sinclair and virtuosi such as Sir Robert Sibbald laid the institutional foundations for the cultivation of natural knowledge in the Enlightenment era and incorporated the sciences of nature into Scotland s emerging public sphere. The restructuring of the Scottish universities in the decades following the Glorious Revolution enhanced the facilities for teaching and research in the sciences and, in doing so, fostered the rise of Newtonianism in Scotland. Newton’s writings inspired innovative work by Colin Maclaurin and other Scottish Newtonians across the many branches of mathematics and natural philosophy and also shaped the methods employed in the nascent ‘science of man’. The compatibility of the Newtonian system with religious belief, in turn, served to solidify the place of natural knowledge in Enlightenment culture, as did the harnessing of such knowledge to economic improvement. Even though the debate over James Hutton s theory of the earth in the 1790s challenged the alliance between science and religion, the natural sciences had by then established themselves as integral and vital components of the Scottish Enlightenment.