It launched July 21, 2003, after raising a $7 million Series A funding round, releasing its first product, and lining up six customers as references, and was backed by venture investors Benchmark Capital and Stanford University.

[9] In 2004, strict new HIPAA regulations governing financial disclosures and the privacy of health care data prompted Proofpoint to begin developing new products that would automatically identify and intercept outbound email containing sensitive information.

[12] Another product introduction in November 2004 included Protection Server 3.0, with Email Firewall and MLX-based Dynamic Reputation Analysis, and the Content Security Suite, plug-in modules designed for scanning outbound messages and their attachments to assist in compliance with data protection regulations such as Sarbanes–Oxley, HIPAA, and Gramm–Leach–Bliley.

In a step towards simpler operational requirements, the Proofpoint Messaging Security Gateway Virtual Edition was released in April 2007.

Proofpoint Messaging Security Gateway V5.0 was released in June 2007, and was based on a new, integrated architecture, combining all its capabilities into a single platform.

ICSA Labs, an independent division of Verizon Business, announced in April 2007, that it had certified six anti-spam products under their new testing program, one of which was the Proofpoint Messaging Security Gateway.

Proofpoint products are designed to solve three business problems: advanced cybersecurity threats, regulatory compliance, and brand-impostor fraud (which it calls "digital risk").

[33] Proofpoint's security portfolio includes products that stop both traditional cyberattacks (delivered via malicious attachments and URLs) and socially engineered attacks—such as business email compromise (BEC) and credential phishing—that do not use malware.

Automated encryption, data-loss prevention and forensics-gathering tools are designed to speed incident response and mitigate the damage and costs of any threats that do get through.

The portfolio also includes protection from social-media account takeovers, harmful mobile apps, and rogue Wi-Fi networks.