Sequencing whole human genomes presents many technical challenges. Whole human genomes have a large number of long repetitive sequence segments of more than 1,000 bp, which cannot be distinguished by short-read instruments. Since it has been reported that each individual human genome has 2.7 to 4.1 million variants, then, for the 3.2 Gigabyte whole human genome, there is at least one variant per every 1,000 bases. These long repetitive sequence segments could include structure alteration and gene mutations relating to diseases, but might not be efficiently and accurately characterized by short-read NGS technologies. To address these challenges, long-read sequencing technologies have been developed and have already provided some astounding applications. For example, in 2014, scientists successfully applied nanopore sequencing technology developed by Oxford Nanopore Technologies (ONT) to monitor the transmission history and disease evolution of the Ebola virus, essentially in real time, during its outbreak. In this installment, we will discuss two of the main long-read sequencing technologies: (i) the synthetic approach and (ii) the single-molecule sequencing approach, and will review the relevant patents.