The generation and handling of the light-sensitive and metastable yellow arsenic (As4) is extremely challenging. In view of recent breakthroughs in synthesizing As4 storage materials and transfer reagents, the more intensive use of yellow arsenic as a source for further reactions can be expected. Given these aspects, the current stage of knowledge of the direct use of As4 is comprehensively summarized in the present review, which lists the activation of As4 by main group elements as well as transition metal compounds (including the f-block elements). Moreover, it also partly compares the reaction outcomes in relation to the corresponding reactions of P4. The possibility of using alternative sources for generating arsenic moieties and compounds is also discussed. The release of As4 molecules from precursor compounds and the use of transfer reagents for polyarsenic entities open up new synthetic pathways to avoid the direct generation of yellow arsenic solutions and to ensure its smooth usage for subsequent reactions.