The sustainable use of marine resources is the key to successful implementation of the blue economy. Seaweed cultivation and seaweed-derived products constitute major pillars of this economy. A number of obstacles hamper the commercial cultivation of seaweeds and thus quality and quantity of seaweed-derived products; one of them is the non-availability of improved germplasm. Seaweed germplasm improvement approaches involve traditional and non-traditional means, which possess specific constrains. The in vitro cultures and regeneration systems are advantageous for the continuous provision of planting stock and compliment the conventional breeding program. The in vitro techniques are known to induce variability and the frequency of these variations varies with the explant types, regeneration pattern, media composition, and cultural conditions. Thus, the efficient in vitro cell/callus culture and propagule regeneration system is the prerequisite for a successful crop improvement program through genetically modified organism (GMO) and non-GMO technologies. This chapter reports an overview of cell and callus culture-mediated propagule regeneration in commercial seaweeds. This chapter focuses on the development of callus and reliable protocol to achieve callus-mediated micropropagule regeneration. Further effects of different factors on in vitro cultures and the potential of these cultures in genetic improvement in seaweeds through high-end biotechnological tools have been discussed. The chapter overviews the progress and updates on in vitro callus and cell culture-mediated propagule regeneration in commercially cultivated seaweeds.