The department of Santa Cruz in Bolivia makes part of the Amazon basin, and it embraces a large portion of the Bolivian lowland forest, with most of its area covered by semideciduous forest. The agricultural development, and hence deforestation in Santa Cruz, does not follow any similar path of other tropical countries of the region, and it is characterized by a productive, high value and profitable agricultural land use. Yet, the agricultural frontier development involving both small and medium and large-scale producers has, since the two last decades, led to an exponential process of deforestation. Forest clearing is currently localized in an area known as being one of the region's major "hot spots" of deforestation. This paper aims at analysing the dynamics of agricultural frontier expansion in Santa Cruz distinguishing different zones with varied ecological, social and economic characteristics. The three main objectives are to illustrate the magnitude and localization of deforestation in Santa Cruz in a three-fold period, to describe the differentiated dynamics of agriculture frontier development linked to diverse actors and geographical settings within the department of Santa Cruz; and to determine the factors that influence on agricultural expansion at the frontier. This study is based on informant interviews, secondary socio-economic information, and satellite remote sensing imagery integrated in a GIS to facilitate land-use change analysis.