There are 2 basic types of organizations out there: products and services. There's are lots of variations of each, but basic principles are the same, one is all about products, the other is all about individual attention (services). Within those 2 models there are some variations. Let's take the Service businesses for example. Some of them require a substantial degree of project management (building a house, creating software), and others require general task tracking (realtors, financial planners, mortgage brokers, insurance agents, consultants..). One can argue that task tracking is a variation on project management, and I would agree, but from the systems point of view, I would keep those separate as they require different solutions.
Now, 37 Signals Highrise provides a solution for Services businesses that are not very project-management intensive (realtors, financial planners, mortgage brokers, insurance agents, consultants..) For these folks, a system like Highrise can replace the stone age ACT! or Goldmine, or perhaps even Outlook. The system has a very slick user interface and is very capable at sharing both the contacts and client-related tasks across the office. It's easy to attach notes and coordinate activities on the contact/client basis.
So overall Highrise gets the kudos for a very sexy UI and a very good contact/task management system for client-driven businesses.
If you have a lot of project-based collaboration, I would recommend Central Desktop (see this review) over Highrise.
If you're doing a lot of email marketing, I would recommend Relenta (see review here)
And finally, if you are a product organization (or want to implement a sales funnel), and looking for something closer to SalesForce.com, I recommend Zoho CRM (review here)