This article is a sequel to the four earlier comprehensive reviews which covered the field of membrane guanylate cyclase from its origin to the year 2002 (Sharma in Mol Cell Biochem 230:3-30, 2002) and then to the year 2004 (Duda et al. in Peptides 26:969-984, 2005); and of the Ca(2+)-modulated membrane guanylate cyclase to the year 1997 (Pugh et al. in Biosci Rep 17:429-473, 1997) and then to 2004 (Sharma et al. in Curr Top Biochem Res 6:111-144, 2004). This article contains three parts. The first part is "Historical"; it is brief, general, and freely borrowed from the earlier reviews, covering the field from its origin to the year 2004 (Sharma in Mol Cell Biochem, 230:3-30, 2002; Duda et al. in Peptides 26:969-984, 2005). The second part focuses on the "Ca(2+)-modulated ROS-GC membrane guanylate cyclase subfamily". It is divided into two sections. Section "Historical" and covers the area from its inception to the year 2004. It is also freely borrowed from an earlier review (Sharma et al. in Curr Top Biochem Res 6:111-144, 2004). Section "Ca(2+)-modulated ROS-GC membrane guanylate cyclase subfamily" covers the area from the year 2004 to May 2009. The objective is to focus on the chronological development, recognize major contributions of the original investigators, correct misplaced facts, and project on the future trend of the field of mammalian membrane guanylate cyclase. The third portion covers the present status and concludes with future directions in the field.