Among natural sources, the green alga Haematococcus pluvialis is the major producer of the potent antioxidant pigment astaxanthin, a high-value compound whose demand is still not sufficiently covered by the current industrial production. Despite the availability of low-cost synthetic astaxanthin, natural astaxanthin is more potent and accepted for human consumption and food additive uses. This review highlights the use of different biotechnological approaches aiming to increase astaxanthin production yields and discusses the advantages and drawbacks of traditional alternatives widely used on other microorganisms. These traditional approaches span from the easy to perform but not devoid of problems random mutagenesis, to advanced methods like microalgae genetic engineering, which has great potential for enhancement, despite being highly restricted in several countries by genetically modified organism legislation. In addition, we propose the underexplored approach of artificial polyploidization for the obtention of strains with increased cell size, which have the advantage of being considered as non-genetically modified organisms that do not require modification of the current industrial production procedures.